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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2014-11-24T00:00:00-05:00" class="date-display-single">November 24, 2014</span></p><div class='syndicate'><h1>Targeting Parkinson’s Disease Pathways</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul class="spaced">
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<li>By blocking mitochondria division, scientists were able to restore function and protect neurons from damage in mouse models of Parkinson’s disease.</li>
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<li>These preliminary research findings suggest a strategy to slow or halt the disease.</li>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=OJaNajjw&timestamp=1431545319 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=fKjefBNm&timestamp=1431545319 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=zBSZSaJh&timestamp=1431545319 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=wyUQg8fJ&timestamp=1431545319 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=x0d6xBPK&timestamp=1431545319 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2014/20141124-parkinsons.jpg?itok=fKjefBNm&timestamp=1431545319" alt="Mitochondia" title="Mitochondia" />
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</picture><span class="caption">Mutant Drp1(left) blocks mitochondrial fission, resulting in longer mitochondria (arrow). Fis1 (right) promotes fission, resulting in smaller mitochondria.</span></div>
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</div><p>Parkinson’s disease develops when brain cells that produce the neurotransmitter dopamine begin to die. Loss of these neurons, and others, leads to involuntary shaking, slowed movements, muscle stiffness, and other problems. Medications can help manage symptoms, but there's no treatment to slow or stop the disease.</p>
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<p>The underlying causes of neuron death in Parkinson’s disease aren’t well understood. Recent studies have linked dysfunctional mitochondria as one of the pathways causing neuron death. These organelles convert compounds derived from food into the molecules that cells use for energy. Studies suggest that proteins involved in the dynamics of these organelles—how they divide (fission), combine (fusion), and move—may play a role in Parkinson’s disease.</p>
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<p>A team led by Dr. Kim Tieu, who was at the University of Rochester School of Medicine and is now at Plymouth University in the UK, explored the effects of manipulating mitochondrial dynamics in 2 mouse models of the disease. One was a genetic model; another used a neurotoxicant that affects mitochondria. The work was funded by NIH’s National Institute of Environmental Health Sciences (NIEHS), National Institute on Aging (NIA), and others. Results appeared in <em>Nature Communications</em> on November 5, 2014.</p>
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||
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||
<p>The scientists tested the effects of blocking or promoting mitochondrial fission by using genetic engineering techniques. To block fission, they used a mutant version of dynamin-related protein 1 (Drp1), a protein involved in fission. To promote fission, they boosted levels of Fission-1 (Fis1), which helps bring Drp1 to mitochondria.</p>
|
||
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||
<p>The Drp1 mutant restored dopamine release and protected neurons in both mouse models, while Fis1 did not. To confirm that blocking mitochondrial fission was causing these benefits, the researchers tested a small molecule called Mitochondrial Division Inhibitor-1 (Mdivi-1). Mdivi-1 is a Drp1 inhibitor that’s been shown to block mitochondrial fission. They found that Mdivi-1 also restored dopamine release and protected neurons in the mice.</p>
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<p>By the time people are diagnosed with Parkinson’s disease, there’s already substantial neuron damage. Thus, the researchers tested the effects of delaying gene or drug delivery until after nerve damage had occurred. They found that mutant Drp1 and mdivi-1 both improved dopamine release even after damage to the neuron pathway responsible for dopamine release. The findings suggest that the underlying cellular pathway that causes Parkinson’s disease might be restored even after neuron damage has progressed.</p>
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<p>“Our findings show exciting potential for an effective treatment for Parkinson’s disease and pave the way for future in-depth studies in this field,” Tieu says. “It’s worth noting that other researchers are also targeting this mitochondrial fission/fusion pathway as potential treatments for other neurological diseases such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.”</p>
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<p>—by Harrison Wein, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.nih.gov/researchmatters/december2013/12092013parkinsons.htm" target="_top">Study Reveals New Targets for Parkinson's Disease</a></li><li><a href="http://www.nih.gov/researchmatters/july2012/07162012parkinsons.htm" target="_top">Skin Cells Yield Clues to Parkinson’s Disease</a></li><li><a href="http://www.nih.gov/researchmatters/may2014/05052014muscle.htm" target="_top">Mitochondrial Fusion May Explain Alcohol’s Effect on Muscle</a></li><li><a href="http://www.ninds.nih.gov/disorders/PD" target="_top">Parkinson's Disease</a></li><li><a href="http://newsinhealth.nih.gov/issue/nov2014/feature2" target="_top">Parkinson’s Disease: Understanding a Complicated Condition</a></li><li><a href="http://www.niehs.nih.gov/health/topics/conditions/parkinson/" target="_top">Parkinson’s Disease and Environmental Factors</a></li><li><a href="http://www.ninds.nih.gov/disorders/mitochondrial_myopathy/mitochondrial_myopathy.htm" target="_top">Mitochondrial Disorders</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/25370169">Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo.</a> Rappold PM, Cui M, Grima JC, Fan RZ, de Mesy-Bentley KL, Chen L, Zhuang X, Bowers WJ, Tieu K. <em>Nat Commun</em>. 2014 Nov 5;5:5244. doi: 10.1038/ncomms6244. PMID: 25370169.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Environmental Health Sciences (NIEHS), National Institute on Aging (NIA), National Center for Advancing Translational Sciences (NCATS), and National Center for Research Resources (NCRR); and the Medical Research Council (UK).</p>
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<div about="/block/research-matters---popular-stori" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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